Race/Ethnicity and the Pharmacogenetics of Reported Suicidality With Efavirenz Among Clinical Trials Participants.

TitleRace/Ethnicity and the Pharmacogenetics of Reported Suicidality With Efavirenz Among Clinical Trials Participants.
Publication TypeJournal Article
Year of Publication2017
AuthorsMollan KR, Tierney C, Hellwege JN, Eron JJ, Hudgens MG, Gulick RM, Haubrich R, Sax PE, Campbell TB, Daar ES, Robertson KR, Ventura D, Ma Q, Edwards DRVelez, Haas DW
Corporate AuthorsAIDS Clinical Trials Group
JournalJ Infect Dis
Volume216
Issue5
Pagination554-564
Date Published2017 Sep 01
ISSN1537-6613
KeywordsAdult, Anti-HIV Agents, Benzoxazines, Continental Population Groups, Cytochrome P-450 CYP2A6, Cytochrome P-450 CYP2B6, Ethnic Groups, Female, Gene Frequency, Genotype, HIV Infections, Humans, Male, Pharmacogenetics, Polymorphism, Single Nucleotide, Proportional Hazards Models, Risk Factors, Suicidal Ideation, Suicide, Treatment Outcome
Abstract

Background: We examined associations between suicidality and genotypes that predict plasma efavirenz exposure among AIDS Clinical Trials Group study participants in the United States.

Methods: Four clinical trials randomly assigned treatment-naive participants to efavirenz-containing regimens; suicidality was defined as reported suicidal ideation or attempted or completed suicide. Genotypes that predict plasma efavirenz exposure were defined by CYP2B6 and CYP2A6 polymorphisms. Associations were evaluated with weighted Cox proportional hazards models stratified by race/ethnicity. Additional analyses adjusted for genetic ancestry and selected covariates.

Results: Among 1833 participants, suicidality was documented in 41 in exposed analyses, and 34 in on-treatment analyses. In unadjusted analyses based on 12 genotype levels, suicidality increased per level in exposed (hazard ratio, 1.11; 95% confidence interval, .96-1.27) and on-treatment 1.16; 1.01-1.34) analyses. In the on-treatment analysis, the association was strongest among white but nearly null among black participants. Considering 3 metabolizer levels (extensive, intermediate and slow), slow metabolizers were at increased risk. Results were similar after baseline covariate-adjustment for genetic ancestry, sex, age, weight, injection drug use history, and psychiatric history or recent psychoactive medication.

Conclusions: Genotypes that predict higher plasma efavirenz exposure were associated with increased risk of suicidality. Strength of association varied by race/ethnicity.

DOI10.1093/infdis/jix248
Alternate JournalJ. Infect. Dis.
PubMed ID28931220
Grant ListK08 MH098794 / MH / NIMH NIH HHS / United States
R01 AI077505 / AI / NIAID NIH HHS / United States
UM1 AI069423 / AI / NIAID NIH HHS / United States
UM1 AI106701 / AI / NIAID NIH HHS / United States